Promoter Methylation of RASSF1A Associates to Adult Secondary Glioblastomas and Pediatric Glioblastomas

Overview

Journal ISRN Neurol

Specialty Neurology

Date 2012 Mar 6

PMID 22389839

Citations 7

Authors

Jorge Munoz

Maria del Mar Inda

Paula Lazcoz

Idoya Zazpe

Xing Fan

Jorge Alfaro

Teresa Tunon

Juan A Rey

Javier S Castresana

Affiliations

Soon will be listed here.

Abstract

While allelic losses and mutations of tumor suppressor genes implicated in the etiology of astrocytoma have been widely assessed, the role of epigenetics is still a matter of study. We analyzed the frequency of promoter hypermethylation by methylation-specific PCR (MSP) in five tumor suppressor genes (PTEN, MGMT, RASSF1A, p14(ARF), and p16(INK4A)), in astrocytoma samples and cell lines. RASSF1A was the most frequently hypermethylated gene in all grades of astrocytoma samples, in cell lines, and in adult secondary GBM. It was followed by MGMT. PTEN showed a slight methylation signal in only one GBM and one pilocytic astrocytoma, and in two cell lines; while p14(ARF) and p16(INK4A) did not show any evidence of methylation in primary tumors or cell lines. In pediatric GBM, RASSF1A was again the most frequently altered gene, followed by MGMT; PTEN, p14 and p16 showed no alterations. Lack or reduced expression of RASSF1A in cell lines was correlated with the presence of methylation. RASSF1A promoter hypermethylation might be used as a diagnostic marker for secondary GBM and pediatric GBM. Promoter hypermethylation might not be an important inactivation mechanism in other genes like PTEN, p14(ARF) and p16(INK4A), in which other alterations (mutations, homozygous deletions) are prevalent.

Citing Articles

Epigenetically inactivated RASSF1A as a tumor biomarker.

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DNA methylation analysis with methylation-sensitive high-resolution melting (MS-HRM) reveals gene panel for glioma characteristics.

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Aberrant promoter methylation of cancer-related genes in human breast cancer.

Wu L, Shen Y, Peng X, Zhang S, Wang M, Xu G Oncol Lett. 2017; 12(6):5145-5155.

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Expression Analysis of Genes Involved in the RB/E2F Pathway in Astrocytic Tumors.

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